hi recent years, many new methods have been invented to treat diseases, however there is still no efficient method to cure diseases such as cancer. Furthermore, gene therapy, as a brand new and revolutionary treatment method, is a potential way to cure intractable diseases such as cancer, angiocardiopathy and congenital immune deficiency, etc. However, the core technology—gene delivery problem always limits the development of gene therapy and clinical trials for a long time, wherein it is undoubtedly crucial for the success of gene therapy to obtain a highly efficient and safe gene vector.
At present, gene transport vectors used globally are mainly divided into two categories: one is viral vector and the other is non-viral vector. The viral gene vector is a vector using the ability of the virus to infect cells, based on the virus to build a vector for carrying gene, and accordingly, the vector that delivers genes not using virus is collectively referred to as non-viral gene vector. Although the viral gene vector has the advantage of high efficiency for gene transport, it has the disadvantages such as high immunogenicity, small capacity, variability and carcinogenicity, etc. However, the non-viral gene vector opens up a new path for gene therapy with its advantages, namely design flexibility, low toxicity, low immunogenicity, low tumorigenesis, easy preparation and capable of achieving cell-specific expression and long-term gene expression. So far, nearly one-third of more than 2,000 cases of the clinical trials of gene therapy have been carried out via non-viral gene vectors. However, there is a certain difference between the transfection efficiency of non-viral gene vector and that of the viral vectors, which is a bottleneck restricting its clinical trials. Developing the non-viral gene vector with high efficiency and low toxicity has become one of the important research topics of gene therapy.
Cationic liposomes as a class of non-viral gene vectors, because of their advantages such as simple preparation, non-immunogenicity, capable of repeating transfection, and easy commercialization, etc., have been rapidly developed in recent years. In 1987, Felgner, et al. (PNAS 1987, 84:7413-7417) for the first time prepared a cationic liposome from a cationic lipid DOTMA to deliver DNA, which pioneered the cationic liposome in the field of gene therapy. The liposome formed by the cationic lipid has a similar structure to that of a biomembrane, and can package an exogenous gene as a vector. Cationic liposomes which are positively charged at a physiological pH, can be self-assembled with negatively charged phosphate groups in a nucleic acid molecule to form liposome/gene complexes by means of an electrostatic interaction, the complexes can be adsorbed on the cell surface by the electrostatic interaction, and thereby introduce the exogenous genes into cells through cell endocytosis or other actions so as to play a therapeutic role of genes. Since 1987, many cationic lipids have been designed and synthesized for nucleic acid delivery (Focus 1993, 15:73-83). However, the existing cationic lipids have high toxicity and their transfection efficiency needing to be improved.
It is well known that carbohydrate compounds are widely distributed in nature with high safety. Sucrose ester prepared by using sucrose as a starting material can form a vesicular or double lamellar structure in the aqueous phase, with good biocompatibility and degradability. However, due to a large number of hydroxyl groups in sucrose, it is difficult to obtain single-structure sucrose ester compound by a chemical synthesis method (J. Am. Oil Chem. Soc. 2014, 91: 1891-1901.). So far, there is no relevant research work about applying sucrose ester-based gene vectors for gene delivery. Therefore, the research and development of sucrose ester based gene vector with good biocompatibility, high efficiency and low cytotoxicity have important scientific significance and economic values for developing gene vectors with independent intellectual property rights.